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Mansfield, Keith G.

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Mansfield

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Keith G.

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Mansfield, Keith G.
Author's Publications: search.filters.isAuthorOfPublication.877e17a7-cd53-4913-b60c-0f6616c8a392

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    Local Replication of Simian Immunodeficiency Virus in the Breast Milk Compartment of Chronically-infected, Lactating Rhesus Monkeys
    (BioMed Central, 2010) Permar, Sallie Robey; Kang, Helen H; Wilks, Andrew B; Mach, Linh V; Carville, Angela A L; Mansfield, Keith G.; Learn, Gerald H; Hahn, Beatrice H; Letvin, Norman Lee
    Breast milk transmission remains a major mode of infant HIV acquisition, yet anatomic and immunologic forces shaping virus quasispecies in milk are not well characterized. In this study, phylogenic analysis of envelope sequences of milk SIV variants revealed groups of nearly identical viruses, indicating local virus production. However, comparison of the patterns and rates of CTL escape of blood and milk virus demonstrated only subtle differences between the compartments. These findings suggest that a substantial fraction of milk viruses are produced by locally-infected cells, but are shaped by cellular immune pressures similar to that in the blood.
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    Non-Human Primate Model of Kaposi's Sarcoma-Associated Herpesvirus Infection
    (Public Library of Science, 2009) Chang, Heesoon; Lee, Jong-Soo; Lee, Hye-Ra; Vieira, Jeffrey; Wachtman, Lynn M; Pearson, Christine; Lee, Steven H; Mansfield, Keith G.; Jung, Jae Ung
    Since Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) was first identified in Kaposi's sarcoma (KS) lesions of HIV-infected individuals with AIDS, the basic biological understanding of KSHV has progressed remarkably. However, the absence of a proper animal model for KSHV continues to impede direct in vivo studies of viral replication, persistence, and pathogenesis. In response to this need for an animal model of KSHV infection, we have explored whether common marmosets can be experimentally infected with human KSHV. Here, we report the successful zoonotic transmission of KSHV into common marmosets (Callithrix jacchus, Cj), a New World primate. Marmosets infected with recombinant KSHV rapidly seroconverted and maintained a vigorous anti-KSHV antibody response. KSHV DNA and latent nuclear antigen (LANA) were readily detected in the peripheral blood mononuclear cells (PBMCs) and various tissues of infected marmosets. Remarkably, one orally infected marmoset developed a KS-like skin lesion with the characteristic infiltration of leukocytes by spindle cells positive for KSHV DNA and proteins. These results demonstrate that human KSHV infects common marmosets, establishes an efficient persistent infection, and occasionally leads to a KS-like skin lesion. This is the first animal model to significantly elaborate the important aspects of KSHV infection in humans and will aid in the future design of vaccines against KSHV and anti-viral therapies targeting KSHV coinfected tumor cells.